Ku86 exists as both a full-length and a protease-sensitive natural variant in multiple myeloma cells

Background: Truncated variants of Ku86 protein have previously been detected in 86% to 100% of freshly isolated patient multiple myeloma (MM) cells. Since, the Ku70/Ku86 heterodimer functions as the regulatory subunit of the DNA repair enzyme, DNA-dependent protein kinase, we have been interested in the altered expression and function of Ku86 variant (Ku86v) proteins in genome maintenance of MM. Results: Although, a number of studies have suggested that truncated forms of Ku proteins could be artificially generated by proteolytic degradation in vitro in human lymphocytes, we now show using whole cell immunoblotting that the RPMI-8226 and SGH-MM5 human MM cell lines consistently express full-length Ku86 as well as a 69-kDa Ku86v; a C-terminus truncated 69-kDa variant Ku86 protein. In contrast, Ku86v proteins were not detected in the freshly isolated lymphocytes as was previously reported. Data also indicates that the Ku86v was not generated as a result of carbohydrate modification but that serine proteases may act on the full-length form of the protein. Conclusion: These data confirm that MM cells contain bona fide Ku86v proteins that were generated intracellularly by a post-transcriptional mechanism, which required proteolytic processing

Pretty Girl Milking Her Cow

One morning when Sol was adorningThe dew painted fragrant roseThe Larks sung their tunes melodiousAnd flowers sweet oders disclosed.\u27Twas near to the foot of a MountainWhere cataracts rapidly flow,I saw that fair artist of nature Called Colleen dhas crutha na mbo.The nightengale vied with the Syrren,The Linnet she sang on each spray,The Dove with the sweetest allurements,And Lambs round the sweet one did play,While Cupid sat there in his chariotWell armed with quiver and Bow,To wound all the hearts that came near to ThisColleen dhas crutha na mbo. \u27Twas on a bright mornin\u27 in summerI first heard his voice spakin\u27 lowAs he said to a colleen beside meWho\u27s that purty girl milking her Cow.Oh many times afther ye met me,An\u27 vowed that I always should be,Your darlin a Chushla, Alanna Ma vourneen A suilish Ma chree.I hav\u27nt the manners or gracesOf the Girls in the world where ye move,I hav\u27nt their beautiful faces,But oh I\u27ve a heart that can love.If it plase ye I\u27ll dress me in satinAn\u27 jewels I\u27ll put on my brow,But oh don\u27t be afther forgettingYour purty girl milking her cow. The Song of O\u27Ruark, Prince of Breffni. To the same air. The Valley lay smiling before me,Where lately I left her behindYet I trembled and something hung o\u27er methat sadden\u27d the joy of my mind.I look\u27d for the lamp which, she told me,Should shine, when her Pilgrim return\u27d;But, tho\u27 darkness began to enfold me,No lamp from the battlements burn\u27d! I flew to her chamber \u27twas lonelyAs if the lov\u27d tenant lay dead!Ah, would it were death, and death only!But no, the young false one had fled.And there hung the lute that could softenMy very worst pains in to bliss While the hand that had wak\u27d it so often,Now throbb\u27d to my proud rival\u27s kiss. There was a time, falsest of women!When Breffni\u27s good sword would have sought That man, thro\u27 a million of foemen,Who dar\u27d but to doubt thee in thought!While now, O degenerate daughter,Of Erin, how fall\u27n is thy fame!And, thro\u27 ages of bondage and slaughter,Thy country shall bleed for thy shame. I flew to her chamber \u27twas lonelyAs if the lov\u27d tenant lay dead!Ah, would it were death, and death only!But no, the young false one had fled.And here hung the lute that could softenMy very worst pains in to blissWhile the hand that had wak\u27d it so often,Now throbb\u27d to my proud rival\u27s kiss. Already, the curse is upon her,And strangers her vallies profaneThey come to divide to dishouourAnd tyrants they long will remain!But onward! the green banner rearing,Go, flest ev\u27ry sword to the hilt!On our side is Virtue and Erin,On theirs is the Saxon and Guilt

Use of ultraviolet-light irradiated multiple myeloma cells as immunogens to generate tumor-specific cytolytic T lymphocytes

10.1186/1476-8518-6-2Journal of Immune Based Therapies and Vaccines6

Use of Ultraviolet Light Irradiated Multiple Myeloma Cells as Immunogens to generate Tumor Specific Cytolytic T Lymphocytes

Background: As the eradication of tumor cells in vivo is most efficiently performed by cytolytic Tlymphocytes (CTL), various methods for priming tumor-reactive lymphocytes have been developed. In this study, a method of priming CTLs with ultraviolet (UV)-irradiated tumor cells, which results in termination of tumor cell proliferation, apoptosis, as well as upregulation of heat shock proteins (HSP) expression is described. Methods: Peripheral blood mononuclear cells (PBMC) were primed weekly with UV-irradiated or mitomycin-treated RPMI 8226 multiple myeloma cells. Following three rounds of stimulation over 21 days, the lymphocytes from the mixed culture conditions were analyzed for anti-MM cell reactivity. Results: By day 10 of cultures, PBMCs primed using UV-irradiated tumor cells demonstrated a higher percentage of activated CD8+/CD4- T lymphocytes than non-primed PBMCs or PBMCs primed using mitomycin-treated MM cells. Cytotoxicity assays revealed that primed PBMCs were markedly more effective (p \u3c 0.01) than non-primed PBMCs in killing RPMI 8226 MM cells. Surface expression of glucose regulated protein 94 (Grp94/Gp96) and Grp78 were both found to be induced in UV-treated MM cells. Conclusion: Since, HSP-associated peptides are known to mediate tumor rejection; these data suggest that immune-mediated eradication of MM cells could be elicited via a UV-induced HSP process. The finding that the addition of 17-allylamide-17-demethoxygeldanamycin (17AAG, an inhibitor of HSP 90-peptide interactions) resulted in decreased CTL-induced cytotoxicity supported this hypothesis. Our study, therefore, provides the framework for the development of anti-tumor CTL cellular vaccines for treating MM using UV-irradiated tumor cells as immunogens

Organisational arrangement of human resources management in organisations operating in Slovakia and Czech Republic

A necessary condition of effective functioning of human resources management in an organisation is the creation of adequate organisational conditions including the existence of a human resources management department, its size, composition and responsibility, which are formed following particular conditions of the given organisation. Competitive environment of organisations operating in Slovakia and Czech Republic is growing with the process of world economy globalisation, and it brings the need of flexibility in management, and therefore we have to get used to changes also in the sphere of human resources management, and learn to cope with new impulses and situations. At present, that predominantly includes spreading effects of global financial and economic crisis, influencing all spheres of life in Slovakia and in Czech Republic too. Handling this situation presupposes flexibility in assessment of changes in environment where organisations operate, ability to detect all positive as well as negative impacts and situations, and formulation of measures to enhance their own position sensibly and cautiously. Due to the need of focusing of organisations on comprehensive arrangement of human resources management, in questionnaire researches, we focused on finding out whether and to what extent organisations operating in Slovakia (n = 340) and in Czech Republic (n = 109) focus on human resources management arrangement. The objective of the article is to compare results in the sphere of human resources in organisations operating in Slovak and Czech Republics. The results show that 67% organisations in Slovakia and only 43% in the Czech Republic had a human resources management department which realised followed human resources management functions and personnel strategy

Multiple shifts: new views on pathways and mechanisms of grammaticalization in the English noun phrase

© John Benjamins Publishing Company. In this paper we report on a historical corpus study of English multiple, an adjective which underwent a process of grammaticalization starting from lexical uses with the meaning 'composite', e.g. HR 3617 is a multiple star, to grammaticalized uses as individualizer, paraphrasable as 'different', e.g. She has to perform multiple tasks at the same time, and as quantifier 'several', e.g. I have multiple friends in high society. Multiple is just one of several adjectives going down this path of grammaticalization. However, as we show in this paper, the trajectory of each adjective includes different micro-processes of change. New diachronic case studies on the grammaticalization of individual items thus remain crucial to further advancing our understanding of the potential environments and changes underlying grammaticalization processes. The case of multiple shows that, firstly, not only attributes, but also classifiers can serve as input for grammaticalization, and that, secondly, grammaticalization and lexicalization processes can have non-adjacent functions in the noun phrase as their input and output.status: publishe

Actions of Calcium on Smooth Muscle a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72185/1/j.1749-6632.1988.tb33358.x.pd